Overview
Supervisor
Teije Corneel Middelkoop
Project description
Cell polarization is essential for many biological processes such as asymmetric cell division, cell migration and body axis establishment, and can be observed throughout the tree of life. Cell polarization can be achieved 1) biochemically, via networks of interacting polarity proteins, 2) mechanically, via active transport of components from one side of the cell to another, or 3) mechanochemically, by the integration of biochemical and mechanical control mechanisms. In the past decades, much has been learned about the mechanochemistry underlying cell polarization in various biological contexts. However, it is still entirely unclear how the mechanochemical mechanisms underlying cell polarization evolve, thereby giving rise to different ways by which cells polarize.
The main goal of this PhD project is to understand how mechanochemically-driven cell polarization evolves.
You will focus on polarization of the C. elegans one-cell embryo, which is essential for establishment of one of the main body axes. This polarization event involves the integration of interacting polarity proteins with movements of the actomyosin cytoskeleton (refs 1-3). To understand how this mechanochemical cell polarization mechanism evolves, you will employ experimental evolution and study morphogenesis in C. elegans populations evolving in the lab. Importantly, our preliminary results show that this approach is feasible as we observed evolutionary adaptation already within 20-30 generations (2-3 months). Every 20-30 generations you will 1) measure the population fitness, 2) conduct a biophysical characterization of cell polarization using quantitative fluorescence live imaging, and 3) conduct a genetic characterization of evolving populations by performing whole genome sequencing.
Altogether, this interdisciplinary approach links genomic analysis and biophysical phenotypic analysis with fitness analysis and will therefore provide an in-depth characterization of the evolution of cell polarity. This will pave the way towards understanding how the vast diversity of cell polarization mechanisms evolved.
Candidate profile
Candidate should have a master’s degree in biology, chemistry, engineering or physics. Experience with any of the following methodologies is considered positively, but is not a requirement: live cell microscopy, image analysis, whole genome sequencing, physical/mathematical modeling, coding in Python and/or Matlab.
Suggested reading
Gross P, Kumar KV, Goehring NW, Bois JS, Hoege C, Jülicher F, Grill SW. Guiding self-organized pattern formation in cell polarity establishment. Nat Phys. 2019 15(3):293-300.
Middelkoop TC, Garcia-Baucells J, Quintero-Cadena P, Pimpale L, Yazdi S, Sternberg P, Gross P, Grill SW: CYK-1/Formin activation in cortical RhoA signaling centers promotes organismal left-right symmetry breaking. PNAS 2021 118(20):e2021814118.
Delattre M, Goehring NW. The first steps in the life of a worm: Themes and variations in asymmetric division in C. elegans and other nematodes. Curr Top Dev Biol. 2021 144:269-308.
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